Looking to functional characterization of the transcripts selected as diminished in Q3SA compared with Q3SC, the top enriched pathway was p53 signaling (p = 1.63 × 10−4; Figure 4D). This is reinforced by upstream analysis, in which TP53 mRNA was reduced ∼24-fold in the absence of ATM, and 18 of 19 genes predicted to be transcriptionally regulated by p53 were affected (p = 3.46 × 10−5). Other pathways enriched by the reduced transcripts included IGF-1 signaling, acute phase response signaling, and the Wnt/Ca+2 pathway (Figure 4D). Few pathways were enriched in the list of transcripts increased in Q3SA compared with Q3SC, and these had no clear biological interpretation (Figure 4D). Under normal conditions in the absence of ATM stimuli such as double-stranded breaks, the primary cellular effect is a reduction in p53 signaling.
